Many cellular processes require coordinate changes in the organization of actin filaments and microtubules. These include changes in cell shape, cell movement, establishment of cell polarity, spindle formation and nuclear migration. Yet the molecular mechanisms governing these changes and the biochemical nature of the actin-microtubule interrelationship are largely unknown. The specific aim of this proposal is to identify factors in yeast that associate with both the actin and microtubule networks, with the goal of understanding how actin and microtubule organization is coordinately regulated in vivo. The strategy will be to use actin and microtubule affinity chromatography to purity proteins and/or protein complexes that bind to both actin and microtubules, raise antibodies to purified factors, clone the genes encoding these factors, and study their in vivo functions by genetic approaches. Yeast is an ideal organism in which to study the actin-microtubule functional relationship because it provides the unique opportunity to integrate biochemical and genetic strategies to address protein function.